替格瑞洛和阿司匹林双联抗血小板治疗的急性冠状动脉综合征患者出血事件发生情况及危险因素分析

Analysis of occurrence and risk factors of bleeding events in acute coronary syndrome patients treated with ticagrelor combined with aspirin

目的探讨接受替格瑞洛和阿司匹林双联抗血小板治疗的急性冠状动脉综合征(ACS)患者出血事件发生情况及其危险因素。方法研究对象选自2017年1—12月在首都医科大学附属北京安贞医院住院并接受替格瑞洛和阿司匹林双联抗血小板治疗(阿司匹林100 mg/d、替格瑞洛180 mg/d)的ACS患者。收集符合纳入标准(年龄>18岁、用药时间≥1年且有完整随访记录)患者的病历资料进行回顾性分析,根据1年内是否发生出血事件将患者分为出血组和无出血组,比较2组患者性别、年龄、ACS类型、合并疾病、合并用药、经皮冠状动脉介入治疗史、血常规、肝肾功能等基线临床特征,采用logistic回归方法分析发生出血事件的危险因素,计算比值比(OR)及其95%置信区间(CI)。结果纳入分析的患者共180例,男性135例,女性58例;年龄(57±10)岁,范围31~81岁;出血组39例,无出血组141例,出血事件发生率为21.7%。2组患者在性别分布、年龄、合并疾病、经皮冠状动脉介入治疗史和合并用药等方面的差异均无统计学意义(均P>0.05),出血组患者血小板计数明显低于无出血组[(197±49)×109/L比(220±60)×109/L,t=2.254,P=0.025]。出血组39例患者出血发生时间最短者为用药第14天,最长者为用药第12个月,用药3、6和12个月时,出血事件累积发生率分别为12.2%(22/180)、18.3%(33/180)和21.7%(39/180)。出血事件全部为小出血,以皮肤黏膜瘀斑发生率最高,为15.0%(27/180);其次为牙龈出血或鼻出血,为7.2%(13/180);眼底出血发生率为1.7%(3/180),胃肠道出血和血尿发生率均为0.6%(1/180)。多因素logistic回归分析显示,血小板计数低是发生出血事件的独立危险因素(OR=0.991,95%CI:0.984~0.999,P=0.020)。结论ACS患者接受替格瑞洛和阿司匹林双联抗血小板治疗发生出血事件风险较高,但多为小出血。对于血小板计数较低的ACS患者,应谨慎使用该抗血小板治疗方案并做好全程用药监测。

Objective To explore the occurrence and risk factors of bleeding events in acute coronary syndromes(ACS)patients treated with ticagrelor combined with aspirin.Methods The study subjects were selected from ACS patients who were admitted to Beijing Anzhen Hospital,Capital Medical University from January to December 2017 and treated with ticagrelor and aspirin(aspirin 100 mg/d,ticagrelor 180 mg/d).Medical records of the patients who met the inclusion criteria(at age>18 years,with medication duration≥1 year,and with complete follow-up records)were collected and retrospectively analyzed.The patients were divided into bleeding group and non-bleeding group according to whether there were bleeding events within 1 year.Baseline clinical characteristics such as gender,age,type of ACS,comorbidities,combined drugs,history of percutaneous coronary intervention,routine blood parameters,liver and kidney function,and etc.in patients between 2 groups were compared.The risk factors of bleeding events were analyzed using logistic regression method and the odds ratio(OR)and its 95%confidence interval(CI)were calculated.Results A total of 180 patients were entered in the analysis,including 135 males and 58 females,aged(57±10)years,with the range of 31 to 81 years.There were 39 patients in the bleeding group and 141 patients in the non-bleeding group,and the incidence of bleeding events was 21.7%.None of the differences in gender distribution,age,comorbidities,history of percutaneous coronary intervention or combined drugs in patients between the 2 groups were statistically significant(all P>0.05).The platelet count of patients in the bleeding group was significantly lower than that in the non-bleeding group[(197±49)×109/L vs.(220±60)×109/L,t=2.254,P=0.025].The shortest time from medication to the onset of bleeding of the 39 patients in the bleeding group was 14 days and the longest one was 12 months.The cumulative incidences of bleeding events at 3,6,and 12 months of medication were 12.2%(22/180),18.3%(33/180),and 21.7%(39/180),respectively.All bleeding events were minor bleeding,and the skin mucous ecchymosis had the highest incidence,which was 15.0%(27/180),followed by gingival bleeding or nosebleed,which was 7.2%(13/180).The incidence of fundus hemorrhage was 1.7%(3/180)and incidences of gastrointestinal bleeding and hematuria were both 0.6%(1/180).Multivariate logistic regression analysis showed that low platelet count was an independent risk factor for bleeding events[OR=0.991,95%CI:0.984-0.999,P=0.020].Conclusions ACS patients have a relative high risk of bleeding events when treated with ticagrelor combined with aspirin,but most of them were minor.For ACS patients with low platelet counts,this anti-platelet regimen should be used with caution and drug monitoring should be done in the whole course.